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  1. Article ; Online: Letter to the Editor From Tayek and Umpierrez: "New Onset or Stress Hyperglycemia and Hospital Mortality Risk".

    Tayek, John A / Umpierrez, Guillermo E

    The Journal of clinical endocrinology and metabolism

    2023  Volume 109, Issue 4, Page(s) e1367

    MeSH term(s) Humans ; Hospital Mortality ; Hyperglycemia
    Language English
    Publishing date 2023-11-22
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 3029-6
    ISSN 1945-7197 ; 0021-972X
    ISSN (online) 1945-7197
    ISSN 0021-972X
    DOI 10.1210/clinem/dgad679
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Solumedrol Treatment for Severe Sepsis in Humans with a Blunted Adrenocorticotropic Hormone-Cortisol Response: A Prospective Randomized Double-Blind Placebo-Controlled Pilot Clinical Trial.

    Birudaraju, Divya / Hamal, Sajad / Tayek, John A

    Journal of intensive care medicine

    2021  Volume 37, Issue 5, Page(s) 693–697

    Abstract: Purpose: To test the benefits of Solumedrol treatment in sepsis patients with a blunted adrenocorticotropic hormone (ACTH)-cortisol response (delta <13 µg/dL) with regard to the number of days on ventilator, days on intravenous blood pressure support, ... ...

    Abstract Purpose: To test the benefits of Solumedrol treatment in sepsis patients with a blunted adrenocorticotropic hormone (ACTH)-cortisol response (delta <13 µg/dL) with regard to the number of days on ventilator, days on intravenous blood pressure support, length of time in an intensive care unit (ICU), 14-day mortality, and 28-day mortality. The trial was prospective, randomized, and double-blind. As part of a larger sepsis trial, 54 patients with sepsis had an intravenous ACTH stimulation test using 250 µg of ACTH, and serum cortisol was measured at times 0, 30, and 60 min. Eleven patients failed to increase their cortisol concentration above 19.9 µg/dL and were excluded from the clinical trial as they were considered to have adrenal insufficiency. The remaining 43 patients had a baseline cortisol of 32 ± 1 µg/dL increased to 38 ± 3 µg/dL at 30 min and 40 ± 3 at 60 min. All cortisol responses were <12.9 µg/dL between time 0 and time 60, which is defined as a blunted cortisol response to intravenous ACTH administration. Twenty-one were randomized to receive 20 mg of intravenous Solumedrol and 22 were randomized to receive a matching placebo every 8 h for 7-days. There was no significant difference between the two randomized groups. Data analysis was carried out bya two-tailed test and
    Results: The mean age was 51 ± 2 (mean ± SEM) with 61% female. Groups were well matched with regard to APACHE III score in Solumedrol versus placebo (59 ± 6 vs 59 ± 6), white blood cell count (18.8 ± 2.2 vs 18.6 ± 2.6), and incidence of bacteremia (29 vs 39%). The 28-day mortality rate was reduced in the Solumedrol treated arm (43 ± 11 vs 73 ± 10%;
    MeSH term(s) Adrenocorticotropic Hormone ; Female ; Humans ; Hydrocortisone/therapeutic use ; Male ; Methylprednisolone Hemisuccinate ; Middle Aged ; Prospective Studies ; Sepsis
    Chemical Substances Methylprednisolone Hemisuccinate (5GMR90S4KN) ; Adrenocorticotropic Hormone (9002-60-2) ; Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2021-09-13
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 632828-3
    ISSN 1525-1489 ; 0885-0666
    ISSN (online) 1525-1489
    ISSN 0885-0666
    DOI 10.1177/08850666211038883
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Weight loss and diabetes are new risk factors for the development of invasive aspergillosis infection in non-immunocompromized humans.

    Ghanaat, Farhad / Tayek, John A

    Clinical practice (London, England)

    2018  Volume 14, Issue 5 Spec Iss, Page(s) 296–301

    Abstract: Well-established risk factors for aspergillosis include HIV, cancer, recent corticosteroid (prednisone) therapy, chemotherapy, or thoracic surgery. Non-established risk factors may include weight loss and a history of diabetes. Twenty-three patients ... ...

    Abstract Well-established risk factors for aspergillosis include HIV, cancer, recent corticosteroid (prednisone) therapy, chemotherapy, or thoracic surgery. Non-established risk factors may include weight loss and a history of diabetes. Twenty-three patients without the classical risk factors for IA were identified retrospectively at Harbor UCLA Medical Center by discharge diagnosis over a 20 year period (1992-2012). None of the well-known risk factors are for Invasive Apergillious (IA). A history of weight loss was seen in 66% of the patients with IA (15 of 23). The weight loss ranged from 3.3 lbs to 43 lbs. In patients with weight loss the average loss was 22±3 lbs (mean±SEM). In this small group of patients with IA, diabetes was seen in 8 of the 23 (34%), which is significantly higher than the 19% incidence of diabetes seen in 100 patients with severe sepsis (p<0.05). Likewise, the 34% incidence of diabetes was higher than the 21% incidence reported in immunocompromised patients with invasive aspergillus (IA) infection (p<0.05). A reduced serum albumin concentration was seen in 33% of the study patients, which was less common than the 87% incidence seen in patients with severe sepsis or candidaemia (54%). Seventeen of the 23 patients had pulmonary involvement. While no one had a well-established risk factor for aspergillious, four patients had alcoholism as a potential risk factor. Eleven of the 23 (48%) died during the hospital stay despite antifungal therapy. Immunocompromised patients are known to have a mortality rate of approximately 45% for pulmonary or disseminated disease.
    Conclusion: The incidence of diabetes was greater than seen in immunocompromised patients and may be considered an additional risk factor for the development of aspergillois infection. In addition, a history of weight loss should increase the suspicion for the diagnosis of IA in otherwise a non-immunocompromised patient. Early recognition and treatment of aspergillosis in the non-immunocompromised patient may improve outcome. Weight loss and diabetes should be added to the list of well-known risk factors for invasive aspergillosis and its high mortality rate.
    Language English
    Publishing date 2018-04-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2652272-X
    ISSN 2044-9046 ; 2044-9038
    ISSN (online) 2044-9046
    ISSN 2044-9038
    DOI 10.4172/clinical-practice.1000125
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Identification of integrated proteomics and transcriptomics signature of alcohol-associated liver disease using machine learning.

    Listopad, Stanislav / Magnan, Christophe / Day, Le Z / Asghar, Aliya / Stolz, Andrew / Tayek, John A / Liu, Zhang-Xu / Jacobs, Jon M / Morgan, Timothy R / Norden-Krichmar, Trina M

    PLOS digital health

    2024  Volume 3, Issue 2, Page(s) e0000447

    Abstract: Distinguishing between alcohol-associated hepatitis (AH) and alcohol-associated cirrhosis (AC) remains a diagnostic challenge. In this study, we used machine learning with transcriptomics and proteomics data from liver tissue and peripheral mononuclear ... ...

    Abstract Distinguishing between alcohol-associated hepatitis (AH) and alcohol-associated cirrhosis (AC) remains a diagnostic challenge. In this study, we used machine learning with transcriptomics and proteomics data from liver tissue and peripheral mononuclear blood cells (PBMCs) to classify patients with alcohol-associated liver disease. The conditions in the study were AH, AC, and healthy controls. We processed 98 PBMC RNAseq samples, 55 PBMC proteomic samples, 48 liver RNAseq samples, and 53 liver proteomic samples. First, we built separate classification and feature selection pipelines for transcriptomics and proteomics data. The liver tissue models were validated in independent liver tissue datasets. Next, we built integrated gene and protein expression models that allowed us to identify combined gene-protein biomarker panels. For liver tissue, we attained 90% nested-cross validation accuracy in our dataset and 82% accuracy in the independent validation dataset using transcriptomic data. We attained 100% nested-cross validation accuracy in our dataset and 61% accuracy in the independent validation dataset using proteomic data. For PBMCs, we attained 83% and 89% accuracy with transcriptomic and proteomic data, respectively. The integration of the two data types resulted in improved classification accuracy for PBMCs, but not liver tissue. We also identified the following gene-protein matches within the gene-protein biomarker panels: CLEC4M-CLC4M, GSTA1-GSTA2 for liver tissue and SELENBP1-SBP1 for PBMCs. In this study, machine learning models had high classification accuracy for both transcriptomics and proteomics data, across liver tissue and PBMCs. The integration of transcriptomics and proteomics into a multi-omics model yielded improvement in classification accuracy for the PBMC data. The set of integrated gene-protein biomarkers for PBMCs show promise toward developing a liquid biopsy for alcohol-associated liver disease.
    Language English
    Publishing date 2024-02-09
    Publishing country United States
    Document type Journal Article
    ISSN 2767-3170
    ISSN (online) 2767-3170
    DOI 10.1371/journal.pdig.0000447
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The durability of oral diabetic medications: Time to A1c baseline and a review of common oral medications used by the primary care provider.

    Cherukuri, Lavanya / Smith, Michael S / Tayek, John A

    Endocrinology, diabetes and metabolism journal

    2018  Volume 2, Issue 3

    Abstract: Introduction: Cost of generic medications has risen more in the past few years than any other time in history. While medical insurance covers much of these costs, health care professionals can better provide medications that have the longest duration of ...

    Abstract Introduction: Cost of generic medications has risen more in the past few years than any other time in history. While medical insurance covers much of these costs, health care professionals can better provide medications that have the longest duration of action when compared to placebo
    Methods: Papers in PubMed were identified with keywords placebo. The study must be at least 2 years in length to evaluate the change in A1c over time. The primary endpoint was time to A1c neutrality (return of A1c to baseline at a maximum dose of single oral agent). A medication would be considered at neutrality if the 95% CI crossed baseline. Time to neutrality was averaged for each medication within the class and each summarized for class effect.
    Results: Effective therapy for the DPP-4 and sulfonylurea classes of medications are 3-4 years as compared to a 5-year time to A1c neutrality for metformin usage. In comparison, the projected time to A1c neutrality was approximately 6-8 years for rosiglitazone and pioglitazone. While only a few studies have been published in the SGLT-2 class of medication, the time to A1c neutrality was also 6-8 years with Canagliflozin and full dosage of Empagliflozin.
    Conclusion: Metformin appears to have a 5-year duration of effect before the A1c returns to baseline. The sulfonylureas and DPP-4 inhibitors class of medications have one of the shortest durability which ranges between 3.3 to 4.4 years. In contrast, the SGLT-2 class of medication and the TZD class of medications has a projected time to A1c neutrality from 6-8 years. Diabetic duration of therapy as compared to placebo should be listed with those medications tested so the provider can choose wisely.
    Language English
    Publishing date 2018-07-08
    Publishing country Sweden
    Document type Journal Article
    ISSN 2002-7354
    ISSN (online) 2002-7354
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Differentiating between liver diseases by applying multiclass machine learning approaches to transcriptomics of liver tissue or blood-based samples.

    Listopad, Stanislav / Magnan, Christophe / Asghar, Aliya / Stolz, Andrew / Tayek, John A / Liu, Zhang-Xu / Morgan, Timothy R / Norden-Krichmar, Trina M

    JHEP reports : innovation in hepatology

    2022  Volume 4, Issue 10, Page(s) 100560

    Abstract: Background & aims: Liver disease carries significant healthcare burden and frequently requires a combination of blood tests, imaging, and invasive liver biopsy to diagnose. Distinguishing between inflammatory liver diseases, which may have similar ... ...

    Abstract Background & aims: Liver disease carries significant healthcare burden and frequently requires a combination of blood tests, imaging, and invasive liver biopsy to diagnose. Distinguishing between inflammatory liver diseases, which may have similar clinical presentations, is particularly challenging. In this study, we implemented a machine learning pipeline for the identification of diagnostic gene expression biomarkers across several alcohol-associated and non-alcohol-associated liver diseases, using either liver tissue or blood-based samples.
    Methods: We collected peripheral blood mononuclear cells (PBMCs) and liver tissue samples from participants with alcohol-associated hepatitis (AH), alcohol-associated cirrhosis (AC), non-alcohol-associated fatty liver disease, chronic HCV infection, and healthy controls. We performed RNA sequencing (RNA-seq) on 137 PBMC samples and 67 liver tissue samples. Using gene expression data, we implemented a machine learning feature selection and classification pipeline to identify diagnostic biomarkers which distinguish between the liver disease groups. The liver tissue results were validated using a public independent RNA-seq dataset. The biomarkers were computationally validated for biological relevance using pathway analysis tools.
    Results: Utilizing liver tissue RNA-seq data, we distinguished between AH, AC, and healthy conditions with overall accuracies of 90% in our dataset, and 82% in the independent dataset, with 33 genes. Distinguishing 4 liver conditions and healthy controls yielded 91% overall accuracy in our liver tissue dataset with 39 genes, and 75% overall accuracy in our PBMC dataset with 75 genes.
    Conclusions: Our machine learning pipeline was effective at identifying a small set of diagnostic gene biomarkers and classifying several liver diseases using RNA-seq data from liver tissue and PBMCs. The methodologies implemented and genes identified in this study may facilitate future efforts toward a liquid biopsy diagnostic for liver diseases.
    Lay summary: Distinguishing between inflammatory liver diseases without multiple tests can be challenging due to their clinically similar characteristics. To lay the groundwork for the development of a non-invasive blood-based diagnostic across a range of liver diseases, we compared samples from participants with alcohol-associated hepatitis, alcohol-associated cirrhosis, chronic hepatitis C infection, and non-alcohol-associated fatty liver disease. We used a machine learning computational approach to demonstrate that gene expression data generated from either liver tissue or blood samples can be used to discover a small set of gene biomarkers for effective diagnosis of these liver diseases.
    Language English
    Publishing date 2022-08-18
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2589-5559
    ISSN (online) 2589-5559
    DOI 10.1016/j.jhepr.2022.100560
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  7. Article ; Online: Voriconazole-Induced Hepatitis via Simvastatin- and Lansoprazole-Mediated Drug Interactions: A Case Report and Review of the Literature.

    Lopez, Jose Luis / Tayek, John A

    Drug metabolism and disposition: the biological fate of chemicals

    2015  Volume 44, Issue 1, Page(s) 124–126

    Abstract: Therapeutic voriconazole concentrations have a narrow window of effectiveness before causing cholestatic hepatitis. After undergoing 1 year of voriconazole therapy for pulmonary aspergillosis, a 44-year-old man began treatment with 30 mg lansoprazole for ...

    Abstract Therapeutic voriconazole concentrations have a narrow window of effectiveness before causing cholestatic hepatitis. After undergoing 1 year of voriconazole therapy for pulmonary aspergillosis, a 44-year-old man began treatment with 30 mg lansoprazole for gastroesophageal reflux symptoms. Within 5 days of starting treatment with lansoprazole, the patient presented with fatigue, jaundice, and cholestatic hepatitis. The hepatitis promptly resolved after stopping lansoprazole treatment. Sixteen months later, the patient was given simvastatin therapy, as recommended by the American Diabetes Association to prevent cardiovascular disease for patients with diabetes who are aged >40 years and have one additional risk factor. Within 2 weeks of taking simvastatin, a 3-hydroxy-3-methylglutaryl CoA reductase (statin) therapy, the patient redeveloped fatigue, jaundice, and cholestatic hepatitis. He described both episodes of fatigue and jaundice similarly in terms of onset and intensity. Voriconazole is metabolized by both CYP2C19 and CYP3A4 isoenzymes. Lansoprazole is an inhibitor of the CYP2C19 isoenzyme. Competition between voriconazole and lansoprazole likely led to increased voriconazole serum concentration and acute cholestatic hepatitis in this patient. Simvastatin inhibits the CYP3A4 isoenzyme. After the patient took 10 mg simvastatin daily for 2 weeks, cholestatic hepatitis occurred. The voriconazole concentration remained elevated (4.1 μg/ml) when measured 15 days after stopping simvastatin. The patient's Naranjo Adverse Drug Reaction Probability Scale score of 7 revealed that the cholestatic hepatitis was probably precipitated by lansoprazole. Likewise, the patient's Naranjo score of 9 also revealed that cholestatic hepatitis was attributable to a definite adverse drug reaction precipitated by the addition of simvastatin to the stable baseline regimen of voriconazole. In a single patient, two different inhibitors of the cytochrome P450 pathway stimulated voriconazole-induced cholestatic hepatitis. Although the major cytochrome P450 pathways for the metabolism and clearance of lansoprazole and simvastatin are different, they both likely contributed to the reduced hepatic clearance of voriconazole in this patient.
    MeSH term(s) Adult ; Antifungal Agents/adverse effects ; Antifungal Agents/pharmacokinetics ; Biotransformation ; Chemical and Drug Induced Liver Injury/diagnosis ; Chemical and Drug Induced Liver Injury/etiology ; Cytochrome P-450 CYP2C19/metabolism ; Cytochrome P-450 CYP2C19 Inhibitors/adverse effects ; Cytochrome P-450 CYP3A/metabolism ; Cytochrome P-450 CYP3A Inhibitors/adverse effects ; Drug Interactions ; Dyslipidemias/diagnosis ; Dyslipidemias/drug therapy ; Gastroesophageal Reflux/diagnosis ; Gastroesophageal Reflux/drug therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Jaundice, Obstructive/chemically induced ; Lansoprazole/adverse effects ; Liver/drug effects ; Liver/enzymology ; Male ; Polypharmacy ; Proton Pump Inhibitors/adverse effects ; Pulmonary Aspergillosis/diagnosis ; Pulmonary Aspergillosis/drug therapy ; Pulmonary Aspergillosis/microbiology ; Simvastatin/adverse effects ; Voriconazole/adverse effects ; Voriconazole/pharmacokinetics
    Chemical Substances Antifungal Agents ; Cytochrome P-450 CYP2C19 Inhibitors ; Cytochrome P-450 CYP3A Inhibitors ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Proton Pump Inhibitors ; Lansoprazole (0K5C5T2QPG) ; Simvastatin (AGG2FN16EV) ; CYP2C19 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; CYP3A4 protein, human (EC 1.14.14.55) ; Voriconazole (JFU09I87TR)
    Language English
    Publishing date 2015-10-26
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.115.066878
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Multifactorial intervention and mortality in type 2 diabetes.

    Tayek, John A

    The New England journal of medicine

    2008  Volume 358, Issue 21, Page(s) 2292; author reply 2292–3

    MeSH term(s) Cardiovascular Diseases/etiology ; Cardiovascular Diseases/prevention & control ; Cholesterol, LDL/blood ; Diabetes Complications/prevention & control ; Diabetes Mellitus/therapy ; Glycated Hemoglobin A ; Humans ; Hypoglycemia/complications ; Risk Factors
    Chemical Substances Cholesterol, LDL ; Glycated Hemoglobin A
    Language English
    Publishing date 2008-05-22
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
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  9. Article ; Online: Stents versus bypass grafting for left main coronary artery disease.

    Tayek, John A

    The New England journal of medicine

    2008  Volume 359, Issue 4, Page(s) 424; author reply 425

    MeSH term(s) Angioplasty, Balloon, Coronary ; Combined Modality Therapy ; Coronary Artery Bypass ; Coronary Disease/mortality ; Coronary Disease/therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Stents
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Language English
    Publishing date 2008-07-24
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Safety of Degludec versus Glargine in Type 2 Diabetes.

    Tayek, John A / Danese, Paul N N / Smith, Michael S

    The New England journal of medicine

    2017  Volume 377, Issue 20, Page(s) 1994–1995

    Language English
    Publishing date 2017--16
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc1712575
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